Multiple associated proteins regulate proteasome structure and function

被引:514
作者
Leggett, DS
Hanna, J
Borodovsky, A
Crosas, B
Schmidt, M
Baker, RT
Walz, T
Ploegh, H
Finley, D [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Australian Natl Univ, John Curtin Sch Med Res, Mol Genet Grp, Canberra, ACT 0200, Australia
关键词
D O I
10.1016/S1097-2765(02)00638-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have identified proteins that are abundant in affinity-purified proteasomes, but absent from proteasomes as previously defined because elevated salt concentrations dissociate them during purification. The major components are a deubiquitinating enzyme (Ubp6), a ubiquitin-ligase (Hu15), and an uncharacterized protein (Ecm29). Ecm29 tethers the proteasome core particle to the regulatory particle. Proteasome binding activates Ubp6 300-fold and is mediated by the ubiquitin-like domain of Ubp6, which is required for function in vivo. Ubp6 recognizes the proteasome base and its subunit Rpn1, suggesting that proteasome binding positions Ubp6 proximally to the substrate translocation channel. ubp6A mutants exhibit accelerated turnover of ubiquitin, indicating that de-ubiquitination events catalyzed by Ubp6 prevent translocation of ubiquitin into the proteolytic core particle.
引用
收藏
页码:495 / 507
页数:13
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